The University of California, San Diego Neuroscience Microscopy Imaging Core has grown to be a centerpiece for neuroscience research within the community, and has resulted in remarkable yields in productivity, expanded scientific scope and the ability to test hypotheses in in vivo settings. This success can be measured in over 40 publications in the neuroscience field that have critically relied on the Core to provide expertise in just the short time that it has been in existence. The Core currently has five imaging systems that provide confocal, deconvolution, spinning disk, two-photon and laser dissection microscopy and an onsite microscopist to make maximum use of the tools. The Core provides neuroscientists flexible platforms to determine the ideal imaging modality for specific applications, and provides training opportunities in a broad array of modern imaging tools. In this application, we seek to expand the scope to include several new NINDS-funded Major Users, and acquire two new imaging systems that will greatly benefit our dynamic community and address the major deficiencies of the facility: 1. Confocal imaging with the ability to perform photoinduced conversion in real- time. 2. High-throughput imaging through multi-well live cell microscopy. The requested systems were chosen because of their high image quality, unsurpassed abilities to visualize events in neural systems that were not previously possible, and their ease of use, which is critical for a facility with over 100 regular users. The research that this equipment will support includes studies of neuronal stem cell differentiation, migration, axon guidance, injury repair, stroke, hypoxia, degenerative disease and disordered development that has important implications for understanding and treatment of nervous system disease. The Core draws off of the expertise of the larger UCSD Medical School Imaging Core that combines other complementary tools. The flexibility, dynamic range, sensitivity and image processing capabilities with the proposed tools are essential for the next phase of the NINDS-funded work. Public Health Relevance: This application proposes to advance microscopy imaging capabilities at the University of California, San Diego School of Medicine in a host of areas within cellular neuroscience. The work to be supported by this application will provide imaging tools for over 17 different NINDS R-awards from 12 Major User and other investigators working in areas that the NINDS has already determined to be important.